Lsh Is Essential for Maintaining Global DNA Methylation Levels in Amphibia and Fish and Interacts Directly with Dnmt1.

Eukaryotic genomes are methylated at cytosine bases in the context of CpG dinucleotides, a pattern which is maintained through cell division by the DNA methyltransferase Dnmt1. Dramatic methylation losses are observed in plant and mouse cells lacking Lsh (lymphoid specific helicase), predominantly a...

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Publicado en:BioMed Research International Vol. 2015; pp. 1 - 13
Autores principales: Dunican, Donncha S., Pennings, Sari, Meehan, Richard R.
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 9/28/2015
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 9/28/2015
      vid: 2015
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2015/740637
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        atl: Lsh Is Essential for Maintaining Global DNA Methylation Levels in Amphibia and Fish and Interacts Directly with Dnmt1.
      aug:
        au:
          Dunican, Donncha S.
          Pennings, Sari
          Meehan, Richard R.
        affil: MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
      sug:
        subj:
          DNA Metabolism
          Fish
          Vertebrates
          Enzymes Metabolism
          In Vitro Studies
          Animal Studies
          Tissue Culture Techniques
          RNA
          Blotting, Western
          Funding Source
      ab: Eukaryotic genomes are methylated at cytosine bases in the context of CpG dinucleotides, a pattern which is maintained through cell division by the DNA methyltransferase Dnmt1. Dramatic methylation losses are observed in plant and mouse cells lacking Lsh (lymphoid specific helicase), predominantly at repetitive sequences and gene promoters. However, the mechanism by which Lsh contributes to the maintenance of DNA methylation is unknown. Here we show that DNA methylation is lost in Lsh depleted frog and fish embryos, both of which exhibit developmental delay. Additionally, we show that both Lsh and Dnmt1 are associated with chromatin and that Lsh knockdown leads to a decreased Dnmt1-chromatin association. Coimmunoprecipitation experiments reveal that Lsh and Dnmt1 are found in the same protein complex, and pulldowns show this interaction is direct. Our data indicate that Lsh is usually diffuse in the nucleus but can be recruited to heterochromatin in a HP1α-dependent manner. These data together (a) show that the role of Lsh in DNA methylation is conserved in plants, amphibian, fish, and mice and (b) support a model in which Lsh contributes to Dnmt1 binding to chromatin, explaining how its loss can potentially lead to perturbations in DNA methylation maintenance.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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